Emergency contraception (EC), indicated for the prevention of pregnancy following unprotected intercourse or a known or suspected contraceptive failure, is a woman's second chance for primary prevention of pregnancy. For decades, various high-dose estrogen-progestin regimens have been prescribed by experienced gynecologists for EC, generally involving the off-label administration of high doses of combined oral contraceptive pills. It is only in the mid-nineteen-nineties that dedicated products appeared, following requests from regulatory agencies and women's groups for properly labelled and packaged preparations. Initially, dedicated products consisted of high-dose estrogen-progestin preparations. In 1999, based on WHO publications of randomized clinical trials demonstrating that 0.75 mg levonorgestrel twice was as effective as combined estrogen-progestin preparations, HRA Pharma's NorLevo® became the first progestin-only EC to be granted a marketing authorization in Western countries. Since that time, several preparations have been approved elsewhere in the world (e.g. Plan B®, Levonelle®, Postinor®), and currently the standard of care for EC within 72 hours of unprotected intercourse is the administration of 1.5 mg of levonorgestrel, either in a single dose or in two 0.75 mg doses taken 12-24 hours apart. A number of countries have granted non-prescription status to these preparations based on levonorgestrel's well-characterized safety profile and limited contraindications.
Although EC with 1.5 mg of levonorgestrel has undoubtedly contributed to the prevention of unwanted pregnancies, it has its limitations in terms of efficacy: its efficacy rate drops significantly with the time elapsed since unprotected intercourse. Reported pregnancy rates from WHO trials rise from approximately 1.5 to 2.6%, respectively, for intake 0 to 24 hrs as compared to intake 48-72 hrs after intercourse. In addition, for a woman who presents for EC more than 72 h after intercourse, the only available method with a proven efficacy is the insertion of a copper intra-uterine device (although not approved or labelled for such use in the United States), although use is limited by both availability and the need for insertion by a skilled health-care professional.
Ulipristal acetate (also referred to as CDB-2914, VA2914, HRP-2000 and RTI 3021-012) is an orally-active selective progesterone receptor modulator (SPRM) that has been developed for emergency contraception. Ulipristal acetate inhibits or delays ovulation in a dose-dependent fashion. In a double-blind non-inferiority trial, ulipristal acetate was shown to be as efficacious as levonorgestrel for preventing pregnancy when used within 72 hours of unprotected intercourse (Creinin et al, Obstetrics & Gynecology 2006; Vol. 108; No. 5: 1089-97).